CA2598234A1 - Inhibition de la proteine-1 apparentee a frizzled induite par l'arni pour le traitement du glaucome - Google Patents
Inhibition de la proteine-1 apparentee a frizzled induite par l'arni pour le traitement du glaucome Download PDFInfo
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- CA2598234A1 CA2598234A1 CA002598234A CA2598234A CA2598234A1 CA 2598234 A1 CA2598234 A1 CA 2598234A1 CA 002598234 A CA002598234 A CA 002598234A CA 2598234 A CA2598234 A CA 2598234A CA 2598234 A1 CA2598234 A1 CA 2598234A1
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- seq
- interfering rna
- nucleotides
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PCT/US2006/009000 WO2006099353A1 (fr) | 2005-03-11 | 2006-03-10 | Inhibition de la proteine-1 apparentee a frizzled induite par l'arni pour le traitement du glaucome |
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CA2598234A1 true CA2598234A1 (fr) | 2006-09-21 |
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JP (2) | JP2008533050A (fr) |
KR (1) | KR20080018858A (fr) |
AU (1) | AU2006223131A1 (fr) |
BR (1) | BRPI0609206A2 (fr) |
CA (1) | CA2598234A1 (fr) |
MX (1) | MX2007010608A (fr) |
WO (1) | WO2006099353A1 (fr) |
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DK1781787T3 (en) | 2004-08-23 | 2017-07-31 | Sylentis Sau | TREATMENT OF EYE DISORDERS FEATURED BY AN INCREASED INTRAOCULAR PRESSURE WITH SIRNAS |
EP1856259A1 (fr) * | 2005-03-11 | 2007-11-21 | Alcon Inc. | Inhibition de la proteine-1 apparentee a frizzled induite par l'arni pour le traitement du glaucome |
GB0521351D0 (en) | 2005-10-20 | 2005-11-30 | Genomica Sau | Modulation of TRPV expression levels |
GB0521716D0 (en) | 2005-10-25 | 2005-11-30 | Genomica Sau | Modulation of 11beta-hydroxysteriod dehydrogenase 1 expression for the treatment of ocular diseases |
US20070202186A1 (en) | 2006-02-22 | 2007-08-30 | Iscience Interventional Corporation | Apparatus and formulations for suprachoroidal drug delivery |
US8197435B2 (en) | 2006-05-02 | 2012-06-12 | Emory University | Methods and devices for drug delivery to ocular tissue using microneedle |
RU2010117178A (ru) * | 2007-10-01 | 2011-11-10 | Алькон Рисерч, Лтд. (Us) | Опосредованная самокомплементарными aav доставка молекул, интерферирующих рнк для лечения или профилактики глазных заболеваний |
US7973019B1 (en) | 2007-10-03 | 2011-07-05 | Alcon Research, Ltd. | Transferrin/transferrin receptor-mediated siRNA delivery |
TW200930405A (en) * | 2007-11-15 | 2009-07-16 | Alcon Res Ltd | Low density lipoprotein receptor-mediated siRNA delivery |
AR069704A1 (es) | 2007-12-18 | 2010-02-10 | Alcon Res Ltd | Sistema de administracion de rnai de interferencia y usos del mismo |
JP5996544B2 (ja) | 2010-10-15 | 2016-09-21 | クリアサイド・バイオメディカル・インコーポレーテッドClearside Biomedical Incorporated | 眼球アクセス用装置 |
WO2012161677A1 (fr) | 2011-05-20 | 2012-11-29 | Alcon Research, Ltd. | Administration de petit arn interférent médié par la transferrine/le récepteur de la transferrine |
WO2013103467A1 (fr) | 2012-01-06 | 2013-07-11 | Alcon Research, Ltd. | Procédé d'administration d'arn interférent et son utilisation correspondante |
GB201215857D0 (en) | 2012-09-05 | 2012-10-24 | Sylentis Sau | siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions |
IN2015DN02699A (fr) | 2012-09-05 | 2015-09-04 | Sylentis Sau | |
CN104884049A (zh) | 2012-11-08 | 2015-09-02 | 克莱尔塞德生物医学股份有限公司 | 用于在人类受试者中治疗眼部疾病的方法和装置 |
MX2015015282A (es) | 2013-05-03 | 2016-02-26 | Clearside Biomedical Inc | Aparatos y metodos para inyeccion ocular. |
US10188550B2 (en) | 2013-06-03 | 2019-01-29 | Clearside Biomedical, Inc. | Apparatus and methods for drug delivery using multiple reservoirs |
US10011837B2 (en) | 2014-03-04 | 2018-07-03 | Sylentis Sau | SiRNAs and their use in methods and compositions for the treatment and/or prevention of eye conditions |
MX2016017028A (es) | 2014-06-20 | 2017-08-07 | Clearside Biomedical Inc | Canula de diametro variable y metodos para el control de la profundidad de insercion para administracion de medicamentos. |
USD750223S1 (en) | 2014-10-14 | 2016-02-23 | Clearside Biomedical, Inc. | Medical injector for ocular injection |
US10390901B2 (en) | 2016-02-10 | 2019-08-27 | Clearside Biomedical, Inc. | Ocular injection kit, packaging, and methods of use |
EP3452165A1 (fr) | 2016-05-02 | 2019-03-13 | Clearside Biomedical, Inc. | Systèmes et méthodes pour l'administration de médicaments par voie ophtalmique |
CN110177527B (zh) | 2016-08-12 | 2022-02-01 | 科尼尔赛德生物医学公司 | 用于调节药剂递送用针的插入深度的装置和方法 |
KR20210120061A (ko) * | 2019-01-29 | 2021-10-06 | 더 리젠트스 오브 더 유니이버시티 오브 캘리포니아 | 신규의 녹내장 치료 방법 |
US20230201371A1 (en) * | 2020-03-19 | 2023-06-29 | Clearside Biomedical, Inc. | Compositions and methods for treating ocular disorders |
WO2023239756A1 (fr) | 2022-06-07 | 2023-12-14 | Generation Bio Co. | Compositions de nanoparticules lipidiques et leurs utilisations |
Family Cites Families (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6506569B1 (en) | 1997-05-30 | 2003-01-14 | Human Genome Sciences, Inc. | Antibodies to human tumor necrosis factor receptor TR10 |
US6506559B1 (en) * | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
EP1147204A1 (fr) * | 1999-01-28 | 2001-10-24 | Medical College Of Georgia Research Institute, Inc. | Composition et methode destinees a l'attenuation in vivo et in vitro de l'expression genique utilisant de l'arn double brin |
DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
US20080166356A9 (en) * | 1999-09-13 | 2008-07-10 | Peter Bodine | Pharmaceutical compositions and methods of using secreted frizzled related protein |
US6326193B1 (en) | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
GB9927444D0 (en) | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
US20070026394A1 (en) * | 2000-02-11 | 2007-02-01 | Lawrence Blatt | Modulation of gene expression associated with inflammation proliferation and neurite outgrowth using nucleic acid based technologies |
AU4176801A (en) * | 2000-02-29 | 2001-09-12 | Alcon Lab Inc | Diagnostics and therapeutics for glaucoma |
DE10012340A1 (de) | 2000-03-14 | 2001-09-20 | Merck Patent Gmbh | Verfahren zur Baeyer-Villiger-Oxidation organischer Carbonylverbindungen |
EP1272630A2 (fr) | 2000-03-16 | 2003-01-08 | Genetica, Inc. | Procedes et compositions d'interference d'arn |
AU2001249622B2 (en) * | 2000-03-30 | 2007-06-07 | Massachusetts Institute Of Technology | RNA sequence-specific mediators of RNA interference |
HU230458B1 (hu) * | 2000-12-01 | 2016-07-28 | Europäisches Laboratorium für Molekularbiologie (EMBL) | Az RNS interferenciát közvetítő kis RNS molekulák |
US20050148530A1 (en) * | 2002-02-20 | 2005-07-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
EP1627061B1 (fr) * | 2001-05-18 | 2009-08-12 | Sirna Therapeutics, Inc. | Interference arn a mediation assuree par l'inhibition de genes au moyen de petit acide nucleique interferent (ansi) modifie chimiquement |
TW201041580A (en) * | 2001-09-27 | 2010-12-01 | Alcon Inc | Inhibitors of glycogen synthase kinase-3 (GSK-3) for treating glaucoma |
DE10230997A1 (de) | 2001-10-26 | 2003-07-17 | Ribopharma Ag | Medikament zur Erhöhung der Wirksamkeit eines Rezeptor-vermittelt Apoptose in Tumorzellen auslösenden Arzneimittels |
EP1463531B1 (fr) * | 2001-12-11 | 2011-09-28 | Fibrogen, Inc. | Procede pour inhiber des processus oculaires |
AU2003225233A1 (en) * | 2002-05-03 | 2003-11-17 | Alcon, Inc. | Diagnosis and treatment of glaucoma and methods for discovering new glaucoma therapeutic agents based on the wnt/ca2+ signaling pathway |
AU2003265978A1 (en) * | 2002-05-03 | 2003-11-17 | Duke University | A method of regulating gene expression |
US20050164907A1 (en) | 2002-05-03 | 2005-07-28 | Clark Abbot F. | Diagnosis and treatment of glaucoma and methods for discovering new glaucoma therapeutic agents based on the wnt/planar cell polarity (pcp) signaling pathway |
WO2004014933A1 (fr) * | 2002-08-07 | 2004-02-19 | University Of Massachusetts | Compositions pour l'interference de l'arn et procedes d'utilisation |
US20040029275A1 (en) | 2002-08-10 | 2004-02-12 | David Brown | Methods and compositions for reducing target gene expression using cocktails of siRNAs or constructs expressing siRNAs |
WO2004022782A2 (fr) | 2002-09-04 | 2004-03-18 | Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | Compositions et methodes d'inhibition a specificite ou declenchement tissulaire de l'expression de genes |
US20040072769A1 (en) * | 2002-09-16 | 2004-04-15 | Yin James Qinwei | Methods for design and selection of short double-stranded oligonucleotides, and compounds of gene drugs |
JP2006507841A (ja) * | 2002-11-14 | 2006-03-09 | ダーマコン, インコーポレイテッド | 機能的siRNAおよび超機能的siRNA |
US20040175732A1 (en) * | 2002-11-15 | 2004-09-09 | Rana Tariq M. | Identification of micrornas and their targets |
WO2004076639A2 (fr) | 2003-02-26 | 2004-09-10 | Wyeth | Compositions et methodes destinees a diagnostiquer et traiter des maladies auto-immunes |
US20050203043A1 (en) * | 2004-01-23 | 2005-09-15 | Dharmacon, Inc. | Identification of toxic nucleotide sequences |
GB0403600D0 (en) | 2004-02-18 | 2004-03-24 | Trinity College Dublin | Methods and reagents for treating disease |
KR101147147B1 (ko) * | 2004-04-01 | 2012-05-25 | 머크 샤프 앤드 돔 코포레이션 | Rna 간섭의 오프 타겟 효과 감소를 위한 변형된폴리뉴클레오타이드 |
TWI401316B (zh) | 2004-12-23 | 2013-07-11 | Alcon Inc | 用於治療青光眼之血清澱粉樣蛋白A的RNAi抑制作用 |
TWI386225B (zh) | 2004-12-23 | 2013-02-21 | Alcon Inc | 用於治療眼睛病症的結締組織生長因子(CTGF)RNA干擾(RNAi)抑制技術 |
TW200639252A (en) | 2005-02-01 | 2006-11-16 | Alcon Inc | RNAi-mediated inhibition of ocular hypertension targets |
EP1856259A1 (fr) | 2005-03-11 | 2007-11-21 | Alcon Inc. | Inhibition de la proteine-1 apparentee a frizzled induite par l'arni pour le traitement du glaucome |
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- 2006-03-10 AU AU2006223131A patent/AU2006223131A1/en not_active Abandoned
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- 2006-03-10 WO PCT/US2006/009000 patent/WO2006099353A1/fr active Application Filing
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US20120178795A1 (en) | 2012-07-12 |
US20060223773A1 (en) | 2006-10-05 |
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US7947660B2 (en) | 2011-05-24 |
US20170073681A1 (en) | 2017-03-16 |
EP1856259A1 (fr) | 2007-11-21 |
WO2006099353A1 (fr) | 2006-09-21 |
US8173617B2 (en) | 2012-05-08 |
KR20080018858A (ko) | 2008-02-28 |
MX2007010608A (es) | 2007-10-19 |
US9550994B2 (en) | 2017-01-24 |
JP2012193197A (ja) | 2012-10-11 |
US20110190381A1 (en) | 2011-08-04 |
US20150307882A1 (en) | 2015-10-29 |
JP2008533050A (ja) | 2008-08-21 |
US9040494B2 (en) | 2015-05-26 |
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